AIDS has reached epidemic proportions worldwide. HIV-2 infection is endemic in West Africa although its course is slower and its transmission less effective. Infection with HIV-2 may be protective against subsequent infection with HIV-1. Also reported is a group of people who are exposed to HIV-1 and HIV-2 yet remained seronegative and who possess HIV-specific CTL activity. CTL have been shown to be an important host defense and is associated with the initial control of viremia during primary HIV-1 infection. The hypothesis to be tested here is that HIV-2 infection elicits cellular immune responses that confer protection from superinfection with HIV-1 and that HIV-2 exposure can lead to protective cellular immune responses rather than persistent infection. Specifically the aims of this study are: 1) To characterize the CTL responses in HIV-2 infected individuals and to determine the cross-reactivity of these responses with HIV-1. 2) To identify immunogenic epitopes recognized by HIV-2 specific CTL and map the epitopes targeted by this response. 3) To determine whether CD8 cells or CTL clones from HIV-2 infected persons can inhibit HIV-1 and HIV-2 replication in vitro. 4) To determine whether HIV exposed, seronegative persons have HIV-specific CTL or CD8 inhibitory responses.